The goal of the proposed research is to elucidate the molecular mechanism whereby an excitable cell exerts a trophic influence on another excitable cell. The work will be carried out in tissue culture using clonal nerve and muscle cell lines. Purified neurotoxins, anti-acetylcholine receptor antibody and two-dimensional gel electrophoresis will be used to investigate the mechanisms whereby a nerve cell regulates the synthesis, degradation and distribution of acetylcholine receptors in the nerve or muscle cell being innervated. Various other muscle specific proteins will be assayed as biochemical correlates of nerve-muscle interaction. Additional probes of ganglionic nicotinic and muscarinic acetylcholine receptors will be used to provide access to these molecules in clonal lines of nerve and muscle. A renewed effort will be made to isolate mutant cell lines of nerve and muscle for investigations into the biochemistry of excitation and interaction of these cells. The interaction of excitable cells in tissue culture will be studied with emphasis on cell specificity and molecular mechanisms involved. The investigation of molecular mechanisms will center on the role of membrane-membrane interaction, and the role of putative trophic factors thought to act on the target cell.